ZBP-89与缺氧信号因子HIF-1α在肝癌细胞中的相关性研究

Correlation between ZBP-89 and Hypoxia Signaling Factor HIF-1α in Hepatoma Cells

目的探讨ZBP-89在肝癌组织中的表达与缺氧诱导因子HIF-1α的相关性,为证实ZBP-89通过抑制HIF-1α/Notch1信号通路降低肝癌干细胞“干性”提供依据。方法选择2016年8月~2018年8月深圳市龙华区人民医院与深圳市人民医院肝胆胰外科120例原发性肝癌患者作为研究对象,收集病理标本,采用免疫组化染色方法来检测肝癌细胞及癌旁组织中ZBP-89、HIF-1α的相关表达,分析二者之间的相关性。结果ZBP-89在肝癌组织中呈现出低表达状态,而在癌旁组织中却呈现出高表达状态,分别为34.17%、62.50%;ZBP-89在癌旁组织中表达高于肝癌组织(P<0.05)。而在肝癌组织细胞中发现ZBP-89的表达与缺氧信号因子HIF-1α的表达呈负相关(P<0.05)。结论ZBP-89很可能为肝癌发生、发展过程中一个潜在的抑癌基因,通过抑制HIF-1α/Notch1通路进而抑制肝癌干细胞增殖、增强肝癌干细胞对化疗药物的敏感性,可能是其发挥抑癌效应的重要机制。

Objective To investigate the correlation between the expression of ZBP-89 in hepatocarcinoma and the hypoxia-inducible factor HIF-1α, and to provide evidence for ZBP-89 to reduce the "dryness" of liver cancer stem cells by inhibiting HIF-1α/Notch1 signaling pathway.Methods From August 2016 to August 2018, 120 patients with primary liver cancer in the Department of Hepatobiliary Surgery of Shenzhen Longhua District People's Hospital and Shenzhen People's Hospital were selected as subjects. Pathological specimens were collected and immunohistochemical staining was used to detect liver cancer cells. The correlation expressions of ZBP-89 and HIF-1α in adjacent tissues were analyzed, and the correlation between them was analyzed. Results ZBP-89 showed low expression status in liver cancer tissues, but high expression status (41/120, 75/120) in adjacent tissues 34.17%, 62.50%, respectively;ZBP-89 in adjacent tissues the expression was higher than that of liver cancer tissues (P<0.05). The expression of ZBP-89 was negatively correlated with the expression of hypoxia signal factor HIF-1α in hepatocarcinoma cells (P<0.05).Conclusion ZBP-89 is likely to be a potential tumor suppressor gene in the development and progression of hepatocarcinoma. It can inhibit the proliferation of hepatocellular carcinoma stem cells and enhance the sensitivity of liver cancer stem cells to chemotherapeutic drugs by inhibiting HIF-1α/Notch1 pathway. An important mechanism of effect.